Exchange transfusion, as a form of therapy, was contrasted with the use of fresh frozen plasma, or supportive care alone, in the management of infants with birth weights of less than 1000 grams, and in infants with severe respiratory distress. Exchange transfusion was demonstrated to significantly reduce mortality in infants with the respiratory distress syndrome but had no benefit for the otherwise healthy infant with a birth weight of less than 1000 grams. In addition, factors regulating erythropoiesis and erythropoietin production were evaluated in infants with and without exchange transfusion. A striking relationship was observed between plasma erythropoietin and the infant's oxygen releasing capacity when measured at a venous oxygen tension of 40 mm Hg. These studies demonstrate that response to anemia, in infants of low birth weight, is governed by oxygen supply and that these infants respond appropriately.